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Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2

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  • Hyun-Jung Choi

    (College of Life Science and Biotechnology, Yonsei University
    Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases, College of Medicine, Yonsei University)

  • Haiying Zhang

    (College of Life Science and Biotechnology, Yonsei University)

  • Hongryeol Park

    (College of Life Science and Biotechnology, Yonsei University)

  • Kyu-Sung Choi

    (College of Life Science and Biotechnology, Yonsei University)

  • Heon-Woo Lee

    (College of Life Science and Biotechnology, Yonsei University)

  • Vijayendra Agrawal

    (College of Life Science and Biotechnology, Yonsei University)

  • Young-Myeong Kim

    (School of Medicine, Kangwon National University)

  • Young-Guen Kwon

    (College of Life Science and Biotechnology, Yonsei University)

Abstract

Angiogenesis is regulated by the dynamic interaction between endothelial cells (ECs). Hippo-Yes-associated protein (YAP) signalling has emerged as a key pathway that controls organ size and tissue growth by mediating cell contact inhibition. However, the role of YAP in EC has not been defined yet. Here, we show expression of YAP in the developing front of mouse retinal vessels. YAP subcellular localization, phosphorylation and activity are regulated by VE-cadherin-mediated-EC contacts. This VE-cadherin-dependent YAP phosphorylation requires phosphoinositide 3-kinase-Akt activation. We further identify angiopoietin-2 (ANG-2) as a potential transcriptional target of YAP in regulating angiogenic activity of EC in vitro and in vivo. Overexpression of YAP-active form in EC enhances angiogenic sprouting, and this effect is blocked by ANG-2 depletion or soluble Tie-2 treatment. These findings implicate YAP as a critical regulator in angiogenesis and provide new insights into the mechanism coordinating junctional stability and angiogenic activation of ECs.

Suggested Citation

  • Hyun-Jung Choi & Haiying Zhang & Hongryeol Park & Kyu-Sung Choi & Heon-Woo Lee & Vijayendra Agrawal & Young-Myeong Kim & Young-Guen Kwon, 2015. "Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2," Nature Communications, Nature, vol. 6(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7943
    DOI: 10.1038/ncomms7943
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    Cited by:

    1. Rui Li & Jingchen Shao & Young-June Jin & Haruya Kawase & Yu Ting Ong & Kerstin Troidl & Qi Quan & Lei Wang & Remy Bonnavion & Astrid Wietelmann & Francoise Helmbacher & Michael Potente & Johannes Gra, 2023. "Endothelial FAT1 inhibits angiogenesis by controlling YAP/TAZ protein degradation via E3 ligase MIB2," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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